ICCBH2019 Poster Presentations (1) (226 abstracts)
An evaluation of the rebound phenomenon during denosumab therapy in children with low turnover osteoporosis
Marie-Eve Robinson 1 , Jinhui Ma 2 , Nasrin Khan 3 , Karine Khatchadourian 4 , Marika Pagé 3 , Victor Konji 3 , Mary Ann Matzinger 5 , Nazih Shenouda 5 , Jacob L. Jaremko 6 , Caroline Zuijdwijk 4 , Stefan Jackowski 3 , David Saleh 7 , Lynn MacLeay 3 , Kerry Siminoski 8 & Leanne M Ward 4
1Shriners Hospital for Children - Canada, McGill University, Montreal, Canada; 2Department of Health Research Methods, Evidence, and Impact, McMaster University, Hamilton, Canada; 3Children’s Hospital of Eastern Ontario Research Institute, Ottawa, Canada; 4Department of Pediatrics, University of Ottawa, Ottawa, Canada; 5Department of Medical Imaging, Children’s Hospital of Eastern Ontario and University of Ottawa, Ottawa, Canada; 6Department of Radiology and Diagnostic Imaging, University of Alberta, Edmonton, Canada; 7Department of Pediatrics, Queen’s University, Kingston, Canada; 8Department of Radiology and Diagnostic Imaging and Department of Medicine, University of Alberta, Edmonton, Canada.
Objectives: Denosumab (Dmab) is a monoclonal antibody targeting RANKL administered by sub-cutaneous injection. Recent reports have raised concern about the ‘rebound phenomenon’ (hypercalcemia and increases in bone turnover markers, BTM) following Dmab in adults, and during treatment in children with osteogenesis imperfecta. The purpose of this report was to explore this phenomenon in children with osteoporosis associated with lower bone turnover.
Methods: In this one-year pilot study (NCT02632916), children 4 to 16 years with low-trauma fractures due to osteoporosis were randomized 1:1 to receive ZA 0.025 mg/kg or Dmab 1 mg/kg every 6 months (two doses). Serum ionized calcium and BTM were collected on the day before each dose (c-telopeptide of type I collagen (CTX), and bone-specific alkaline phosphatase (BSALP)). BTM were expressed as age- and gender-matched z-scores (Z).
Results: Ten children completed the study (four with glucocorticoid-treated Duchenne muscular dystrophy (DMD) and one with juvenile osteoporosis (JO) in each group, all boys). At baseline, the two boys with JO had a bone formation rate/bone surface by trans-iliac biopsies at Z −3.3 and −1.0. In DMD at baseline, the mean ± standard deviation serum CTXZ and BSALPZ were −2.6±0.3 and −2.9±0.6, respectively. There were no episodes of hypercalcemia preceding any treatment doses. CTXZ increased between baseline and six months, or between six and 12 months, in 5/5 boys on Dmab (greatest median change during either time period 22%; range 11, 165%) vs 4/5 on ZA (median change 11%; range 4, 14%). The BSALPZ increased in 3/5 boys on Dmab (median change 3%; range −17, 49%) vs 3/5 (median change 12%, range −6.0, 15). On Dmab, the CTXZ was below −2.0 in all but one patient with DMD (Z −1.7 for this patient) at 12 months, but was above-average (Z+0.3) for the patient with JO.
Discussion: In this pilot study, CTXZ increased above baseline more frequently on Dmab compared with ZA. BTM increases were greatest in the patient with JO on Dmab. In contrast, boys with DMD on Dmab had minimal BTM increases; furthermore, BTM remained low in DMD at 12 months.
Disclosure: Leanne Ward has been a consultant to and participated in clinical trials with Novartis Pharmaceuticals and Amgen Inc.
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ISSN 2052-1219 (online)
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